An injection syringe prior to having an injection needle mounted thereto includes a syringe barrel (cylindrical tube) made from glass or plastic, a movable plunger rod (plunger), a gasket that is attached at a front end portion of the plunger rod, and a top cap attached to a needle mount part of the syringe barrel.
For the gasket, a vulcanized rubber (butyl rubber) has been conventionally used in order to prevent leakage of an injection solution.
All elastomers, including butyl rubbers and silicone rubbers that are the subject of the present invention, have been considered to not have slidability with respect to a contacting object.
Thus, gasket main bodies having a concaved groove were actually manufactured by using materials shown in Table 1, and a sliding resistance of each rubber was measured by performing a later described sliding test after various types of rubber rings were fitted onto the concaved groove.
The rubber gaskets were manufactured to have a length of 2 mm and to be larger than the internal diameter of the syringe barrel by 0.2 mm. The test was performed such that only the sliding resistance of a rubber ring was sensed by preventing the gasket main body from making contact with the inner circumferential surface of the syringe barrel.
As a result, as shown in Table 1, butyl rubber did not slide and other rubbers showed a sliding resistance not smaller than 20 N.
When performing an injection with such a large sliding resistance, if a physician or a nurse is to manually push a plunger rod of an injection syringe, he or she cannot smoothly push the plunger rod.
The requirement for achieving that is a sliding resistance not larger than 8 N at maximum.
In addition, even when an injection syringe is to be mounted on an injection device and a plunger rod of the injection syringe is to be mechanically pushed by the injection device, the plunger rod swill not move smoothly when the sliding resistance is not smaller than 20 N.
Even when mechanical pushing is to be performed by using the injection device, a sliding resistance of not larger than 15 N is required.
Thus, in order to improve inferior slidability of such rubber gaskets with respect to the inner circumferential surface of the syringe barrel, a silicone grease has been conventionally applied on the surface of the gasket and the inner circumferential surface of the syringe barrel. The applied amount of the silicone grease is, for example, not more than 8.0 mg with respect to a syringe barrel having a capacity of 5 cc.
When the silicone grease is applied, the sliding resistance becomes dramatically lower, as low as 5 to 8 N (see Table 1).
TABLE 1Unit: NewtonSliding resistanceSliding resistanceSilicone grease Silicone grease coatingElastomer typecoating absentpresentButyl rubberNo slide movement5 to 8 NNitrile rubberNot smaller than 20 N5 to 8 NUrethane rubberNot smaller than 20 N5 to 8 NFluoro rubberNot smaller than 20 N5 to 8 NSilicone rubberNot smaller than 20 N5 to 8 NEthylene propyleneNot smaller than 20 N5 to 8 NrubberPolyisoprene rubberNot smaller than 20 N5 to 8 NPolybutadiene rubberNot smaller than 20 N5 to 8 NChloroprene rubberNot smaller than 20 N5 to 8 NElastomer (A) of present9 to 11 N(Ultrahigh molecular inventionweight PE aloneElastomer (B) of present4 to 8 N(Ultrahigh molecular inventionweight PE + oil)
Table 1 is a comparison of sliding resistances of various types of elastomers and medical silicone rubbers according to the present invention.
The silicone grease has a dramatic effect for improving the sliding resistance of a rubber gasket with respect to the inner circumferential surface of a syringe barrel.
However, when the silicone grease is applied on the surface of the rubber gasket or the inner circumferential surface of the syringe barrel as described above, the silicone grease directly touches a drug solution inside the syringe barrel. The results, which have been conventionally regarded as problems, are a change in quality caused by the silicone grease reacting with an active ingredient in the drug solution, fine particle contamination of the drug solution with silicon fine particles separated from the silicone grease, and adverse effects to a human body as a result.
In addition, there has been a fear of elution of soluble components contained in the rubber into the drug solution.
In particular, since pre-filled syringes, which have been used more frequently in recent years, are filled with a drug solution in advance, stored over a long period of time, and used under various environments; gaskets of the pre-filled syringes are required to have higher performance than those for ordinary injection syringes.
Examples of capabilities that are required include: (a) the gasket does not change the quality of a drug solution even when being in contact with the drug solution for a long period of time, and can be used safely; (b) ability to ensure a tight seal (liquid leakage-less property of preventing leakage of a drug solution from between the gasket and the syringe, and vapor impermeability of preventing external permeation of water content of the drug solution passed the gasket) with respect to a highly permeable drug solution; and (c) having a slidability equivalent to that of an ordinary injection syringe (the sliding resistance being not larger than 8 N when the plunger rod of the injection syringe is to be manually pushed, and not larger than 15 N when the plunger rod of the injection syringe is to be mechanically pushed with an injection device); etc.
In addition, a pre-filled syringe, which is stored for a long period of time, has been reported with a problem regarding difficulty when being used because the gasket adheres to the inner wall of the syringe barrel when the gasket is kept at a single position and has a tendency to fix to that position to cause an increase in initial motion pressure when an injection is to be performed.
Thus, in an attempt to solve the problem, Patent Literature 1 proposes, as a slidability improvement measure, a combination between a thermoplastic or thermosetting elastic elastomer having a Shore A hardness of 30 to 80 (ordinarily 40 to 50 when butyl rubber is used) and a rigid plastic material (hereinafter, simply referred to as a rigid plastic) such as a medical grade polypropylene having excellent chemical resistance.
More specifically, a proposed gasket is obtained by creating cores having various shapes with an outer diameter that is smaller than the internal diameter of a syringe barrel by using a rigid plastic, and fitting, onto the cores, a ring-shaped elastomeric sleeve made from an elastomer and having “rubber elasticity” for preventing leakage of liquid.
As another example, Patent Literature 2 discloses a gasket formed entirely of a slidable silicone rubber obtained by loading a silicone rubber with a silicone oil and a polyethylene powder, and vulcanizing and molding the silicone rubber.